Packaging Solutions

ABSTRACT

The present invention is directed to new and improved packaging systems for storing ophthalmic devices such as contact lenses and to methods for packaging such ophthalmic devices with solutions to improve the comfort of the lenses during wear. In particular, the present invention is directed to a packaging system for storing an ophthalmic device in an aqueous packaging solution comprising hyaluronic acid or a salt thereof. Such solutions are retained on the surface of an unused lens for extended periods of time, resulting in surface modification that persists in the eye, which may provide significant improvement in the wetting properties of fresh contact lenses used for the first time and, moreover, even several hours after lens insertion, thereby preventing dryness and improving lubricity.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention generally relates to packaging solutions forophthalmic devices such as contact lenses.

2. Description of Related Art

Blister-packs and glass vials are typically used to individually packageeach soft contact lens for sale to a customer. Saline or deionized wateris commonly used to store the lens in the blister-packs, as mentioned invarious patents related to the packaging or manufacturing of contactlenses. Because lens material may tend to stick to itself and to thelens package, packaging solutions for blister-packs have sometimes beenformulated to reduce or eliminate lens folding and sticking. For thisreason, polyvinyl alcohol (PVA) has been used in contact-lens packagingsolutions.

It has been stated that if a lens is thoroughly cleaned beforeinsertion, lacrimal fluid can adequately wet the lens. Furthermore, thedifficulties of adding a surfactant to a packaging solution, includingthe possibility of lowering shelf-life and/or adverse reactions duringheat sterilization, have further limited the use of surfactants in apackaging solution for the purpose of providing any possible or marginaleffect on lens comfort. It is only after a lens has been worn, whenproteins or other deposits have formed on the surface of the lens, thatsurfactants have been used in standard lens-care solutions.

It is highly desirable that contact lens be as comfortable as possiblefor wearers. Manufacturers of contact lenses are continually working toimprove the comfort of the lenses. Nevertheless, many people who wearcontact lenses still experience dryness or eye irritation throughout theday and particularly towards the end of the day. An insufficientlywetted lens at any point in time will cause significant discomfort tothe lens wearer. Although wetting drops can be used as needed toalleviate such discomfort, it would certainly be desirable if suchdiscomfort did not arise in the first place.

U.S. Pat. No. 5,882,687 (“the '687 patent”) discloses a packagecontaining a contact lens suitable for immediate use which comprises (a)a solution comprising a soluble polyanionic component and having aviscosity of less than 50 cps at 25° C., an osmolality of at least about200 mOsm/kg and a pH in the range of about 6 to about 9; (b) at leastone contact lens, and (c) a container for holding the solution andcontact lens sufficient to preserve the sterility of the solution andcontact lens, wherein the solution contains no additional disinfectantcomponent. However, the '687 patent nowhere provides any disclosure ofthe use of hyaluronic acid in a packaging solution.

Accordingly, it would be desirable to provide an improved packagingsystem for an ophthalmic lens such that the lens would be comfortable towear in actual use and allow for extended wear of the lens withoutirritation or other adverse effects to the cornea.

SUMMARY OF THE INVENTION

In accordance with one embodiment of the present invention, a method ofpreparing a package comprising a storable, sterile ophthalmic device isprovided comprising:

(a) immersing an ophthalmic device in an aqueous packaging solutioncomprising hyaluronic acid or a salt thereof, wherein the solution hasan osmolality of at least about 200 mOsm/kg and a pH in the range ofabout 4 to about 9;

(b) packaging the solution and the device in a manner preventingcontamination of the device by microorganisms; and

(c) sterilizing the packaged solution and device.

In accordance with a second embodiment of the present invention, amethod for packaging and storing a contact lens is provided comprising,prior to delivery of the contact lens to the customer-wearer, immersingthe contact lens in an aqueous packaging solution inside a package andheat sterilizing the solution, wherein the aqueous packaging solutioncomprises a sterile ophthalmically safe aqueous solution comprisinghyaluronic acid or a salt thereof, wherein the solution has anosmolality of at least about 200 mOsm/kg and a pH of about 4 to about 9.

In accordance with a third embodiment of the present invention, apackaging system for the storage of an ophthalmic device is providedcomprising a sealed container containing one or more unused ophthalmicdevices immersed in an aqueous packaging solution comprising hyaluronicacid or a salt thereof, wherein the solution has an osmolality of atleast about 200 mOsm/kg, a pH of about 4 to about 9 and is heatsterilized.

In accordance with a fourth embodiment of the present invention, apackaging system for the storage of an ophthalmic device is providedcomprising:

(a) an aqueous packaging solution comprising hyaluronic acid or a saltthereof, wherein the solution has an osmolality of at least about 200mOsm/kg and a pH in the range of about 4 to about 9;

(b) at least one ophthalmic device; and

(c) a container for holding the solution and ophthalmic devicesufficient to preserve the sterility of the solution and ophthalmicdevice, wherein the solution does not contain an effective disinfectingamount of a disinfecting agent.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a packaging system for the storage ofophthalmic devices intended for direct contact with body tissue or bodyfluid. As used herein, the term “ophthalmic device” refers to devicesthat reside in or on the eye. These lenses can provide opticalcorrection, wound care, drug delivery, diagnostic functionality orcosmetic enhancement or effect or a combination of these properties.Representative examples of such devices include, but are not limited to,soft contact lenses, e.g., a soft, hydrogel lens; soft, non-hydrogellens and the like, hard contact lenses, e.g., a hard, gas permeable lensmaterial and the like, intraocular lenses, overlay lenses, ocularinserts, optical inserts and the like. As is understood by one skilledin the art, a lens is considered to be “soft” if it can be folded backupon itself without breaking. Any material known to produce anophthalmic device including a contact lens can be used herein.

It is particularly useful to employ biocompatible materials hereinincluding both soft and rigid materials commonly used for ophthalmiclenses, including contact lenses. The preferred substrates are hydrogelmaterials, including silicone hydrogel materials. Particularly preferredmaterials include vinyl functionalized polydimethylsiloxanescopolymerized with hydrophilic monomers as well as fluorinatedmethacrylates and methacrylate functionalized fluorinated polyethyleneoxides copolymerized with hydrophilic monomers. Representative examplesof substrate materials for use herein include those disclosed in U.S.Pat. Nos. 5,310,779; 5,387,662; 5,449,729; 5,512,205; 5,610,252;5,616,757; 5,708,094; 5,710,302; 5,714,557 and 5,908,906, the contentsof which are incorporated by reference herein.

A wide variety of materials can be used herein, and silicone hydrogelcontact lens materials are particularly preferred. Hydrogels in generalare a well-known class of materials that comprise hydrated, cross-linkedpolymeric systems containing water in an equilibrium state. Siliconehydrogels generally have a water content greater than about 5 weightpercent and more commonly between about 10 to about 80 weight percent.Such materials are usually prepared by polymerizing a mixture containingat least one silicone-containing monomer and at least one hydrophilicmonomer. Typically, either the silicone-containing monomer or thehydrophilic monomer functions as a crosslinking agent (a crosslinkerbeing defined as a monomer having multiple polymerizablefunctionalities) or a separate crosslinker may be employed. Applicablesilicone-containing monomeric units for use in the formation of siliconehydrogels are well known in the art and numerous examples are providedin U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533; 5,034,461; 5,070,215;5,260,000; 5,310,779; and 5,358,995.

Representative examples of applicable silicon-containing monomeric unitsinclude bulky polysiloxanylalkyl(meth)acrylic monomers. An example of abulky polysiloxanylalkyl(meth)acrylic monomer is represented by thestructure of Formula I:

wherein X denotes —O— or —NR—; each R¹ independently denotes hydrogen ormethyl; each R² independently denotes a lower alkyl radical, phenylradical or a group represented by

wherein each R^(2′) independently denotes a lower alkyl or phenylradical; and h is 1 to 10.

Examples of bulky monomers are methacryloxypropyltris(trimethyl-siloxy)silane or tris(trimethylsiloxy)silylpropylmethacrylate, sometimes referred to as TRIS andtris(trimethylsiloxy)silylpropyl vinyl carbamate, sometimes referred toas TRIS-VC and the like.

Such bulky monomers may be copolymerized with a silicone macromonomer,which is a poly(organosiloxane) capped with an unsaturated group at twoor more ends of the molecule. U.S. Pat. No. 4,153,641 discloses, forexample, various unsaturated groups such as acryloxy or methacryloxygroups.

Another class of representative silicone-containing monomers includes,but is not limited to, silicone-containing vinyl carbonate or vinylcarbamate monomers such as, for example,1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; trimethylsilylmethyl vinyl carbonate and the like andmixtures thereof.

Another class of silicon-containing monomers includespolyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), which may have hard-soft-hard blocks like traditionalurethane elastomers. They may be end-capped with a hydrophilic monomersuch as 2-hydroxyethyl methacrylate (HEMA). Examples of such siliconeurethanes are disclosed in a variety or publications, including Lai,Yu-Chin, “The Role of Bulky Polysiloxanylalkyl Methacryates inPolyurethane-Polysiloxane Hydrogels,” Journal of Applied PolymerScience, Vol. 60, 1193-1199 (1996). PCT Published Application No. WO96/31792 discloses examples of such monomers, which disclosure is herebyincorporated by reference in its entirety. Further examples of siliconeurethane monomers are represented by Formulae II and III:

E(*D*A*D*G)_(a) *D*A*D*E′; or   (II)

E(*D*G*D*A)_(a) *D*A*D*E′; or   (III)

wherein:

D independently denotes an alkyl diradical, an alkyl cycloalkyldiradical, a cycloalkyl diradical, an aryl diradical or an alkylaryldiradical having 6 to about 30 carbon atoms;

G independently denotes an alkyl diradical, a cycloalkyl diradical, analkyl cycloalkyl diradical, an aryl diradical or an alkylaryl diradicalhaving 1 to about 40 carbon atoms and which may contain ether, thio oramine linkages in the main chain;

* denotes a urethane or ureido linkage;

a is at least 1;

A independently denotes a divalent polymeric radical of Formula IV:

wherein each R^(s) independently denotes an alkyl or fluoro-substitutedalkyl group having 1 to about 10 carbon atoms which may contain etherlinkages between the carbon atoms; m′ is at least 1; and p is a numberthat provides a moiety weight of about 400 to about 10,000;

each of E and E′ independently denotes a polymerizable unsaturatedorganic radical represented by Formula V:

wherein: R³ is hydrogen or methyl;

-   R⁴ is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a    —CO—Y—R⁶ radical wherein Y is —O—, —S— or —NH—;-   R⁵ is a divalent alkylene radical having 1 to about 10 carbon atoms;-   R⁶ is a alkyl radical having 1 to about 12 carbon atoms;-   X denotes —CO— or —OCO—;-   Z denotes —O— or —NH—;-   Ar denotes an aromatic radical having about 6 to about 30 carbon    atoms;-   w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A preferred silicone-containing urethane monomer is represented byFormula VI:

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 andpreferably is 1, p is a number which provides a moiety weight of about400 to about 10,000 and is preferably at least about 30, R⁷ is adiradical of a diisocyanate after removal of the isocyanate group, suchas the diradical of isophorone diisocyanate, and each E″ is a grouprepresented by:

In another embodiment of the present invention, a silicone hydrogelmaterial comprises (in bulk, that is, in the monomer mixture that iscopolymerized) about 5 to about 50 percent, and preferably about 10 toabout 25, by weight of one or more silicone macromonomers, about 5 toabout 75 percent, and preferably about 30 to about 60 percent, by weightof one or more polysiloxanylalkyl (meth)acrylic monomers, and about 10to about 50 percent, and preferably about 20 to about 40 percent, byweight of a hydrophilic monomer. In general, the silicone macromonomeris a poly(organosiloxane) capped with an unsaturated group at two ormore ends of the molecule. In addition to the end groups in the abovestructural formulas, U.S. Pat. No. 4,153,641 discloses additionalunsaturated groups, including acryloxy or methacryloxy.Fumarate-containing materials such as those disclosed in U.S. Pat. Nos.5,310,779; 5,449,729 and 5,512,205 are also useful substrates inaccordance with the invention. Preferably, the silane macromonomer is asilicon-containing vinyl carbonate or vinyl carbamate or apolyurethane-polysiloxane having one or more hard-soft-hard blocks andend-capped with a hydrophilic monomer.

Suitable hydrophilic monomers include amides such as dimethylacrylamideand dimethylmethacrylamide, cyclic lactams such as n-vinyl-2-pyrrolidoneand poly(alkene glycols) functionalized with polymerizable groups.Examples of useful functionalized poly(alkene glycols) includepoly(diethylene glycols) of varying chain length containingmonomethacrylate or dimethacrylate end caps. In a preferred embodiment,the poly(alkene glycol) polymer contains at least two alkene glycolmonomeric units. Still further examples are the hydrophilic vinylcarbonate or vinyl carbamate monomers disclosed in U.S. Pat. No.5,070,215, and the hydrophilic oxazolone monomers disclosed in U.S. Pat.No. 4,910,277. Other suitable hydrophilic monomers will be apparent toone skilled in the art.

In one embodiment, the lens can be a Group II and Group IV lens having awater content greater than about 50% by weight, preferably about 55% toabout 80% water. High water content is associated with materials havinghigh oxygen permeability, resulting in the increasing popularity of suchlenses, including especially disposable and planned-replacement lenses.Group IV materials include, but are not limited to, bufilcon A,etafilcon A, methafilcon A, ocufilcon C, perfilcon A, phemfilcon A, andvifilcon A. Materials containing methacrylic acid monomers includemethafilcon B, ocufilcon D, methafilcon A, and etafilcon A (USAN and theUSAP Dictionary of Drug Names). Group II materials include, by way ofexample only, lidofilcon A or B, alphafilcon A, Sauflon, Hydron, etc.,which materials typically contain primarily HEMA and N-vinylpyrrolidone(NVP). DMA (N,N-dimethylacrylamide) is another Group II monomer that maybe used in Group II lens materials to provide hydrophilicity.

The above silicone materials are merely exemplary, and other materialsfor use as substrates that can benefit by being packaged in thesolutions according to the present invention and have been disclosed invarious publications and are being continuously developed for use incontact lenses and other medical devices can also be used. For example,an ophthalmic lens for use herein can be a cationic lens such as acationic contact lens or fluorinated silicone-containing monomers. Suchmonomers have been used in the formation of fluorosilicone hydrogels toreduce the accumulation of deposits on contact lenses made therefrom, asdisclosed in, for example, U.S. Pat. Nos. 4,954,587; 5,010,141 and5,079,319. The use of silicone-containing monomers having certainfluorinated side groups, i.e., —(CF₂)—H, have been found to improvecompatibility between the hydrophilic and silicone-containing monomericunits. See, e.g., U.S. Pat. Nos. 5,321,108 and 5,387,662.

In another embodiment, the present invention is also directed to acontact lens for extended-wear or specialty uses, such as for relativelythick lenses. Extended lenses are lenses capable of being wornovernight, preferably capable of being worn for at least one week, mostpreferably capable of wear for a continuous period of one week to onemonth. By “capable” is meant lenses approved by one or more governmentalregulatory authorities for such consumer use, for example, the U.S. Food& Drug Administration (USFDA) in the U.S. or its equivalent in othercountries.

Extended-wear lenses require relatively high oxygen permeability. Theoxygen-permeability is the rate at which oxygen will pass through amaterial. The oxygen-permeability Dk of a lens material does not dependon lens thickness. Oxygen permeability is measured in terms of barrerswhich have the following units of measurement:

On the other hand, the oxygen transmissibility of a lens, as usedherein, is the rate at which oxygen will pass through a specific lens.Oxygen transmissibility, Dk/t, is conventionally expressed in units ofbarrers/mm, where t is the average thickness of the material (in unitsof mm) over the area being measured. For example, a lens having a Dk ofabout 90 barrers (oxygen-permeability barrers) and a thickness of about90 microns (about 0.090 mm) would have a Dk/t or about 100 barrers/mm(oxygen transmissibility barrers/mm).

Ophthalmic devices such as contact lenses for application of the presentinvention can be manufactured employing various conventional techniques,to yield a shaped article having the desired posterior and anterior lenssurfaces. Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429and 3,660,545; preferred static casting methods are disclosed in U.S.Pat. Nos. 4,113,224 and 4,197,266. Curing of the monomeric mixture isoften followed by a machining operation in order to provide a contactlens having a desired final configuration. As an example, U.S. Pat. No.4,555,732 discloses a process in which an excess of a monomeric mixtureis cured by spincasting in a mold to form a shaped article having ananterior lens surface and a relatively large thickness. The posteriorsurface of the cured spincast article is subsequently lathe cut toprovide a contact lens having the desired thickness and posterior lenssurface. Further machining operations may follow the lathe cutting ofthe lens surface, for example, edge-finishing operations.

After producing a lens having the desired final shape, it is desirableto remove residual solvent from the lens before edge-finishingoperations. This is because, typically, an organic diluent is includedin the initial monomeric mixture in order to minimize phase separationof polymerized products produced by polymerization of the monomericmixture and to lower the glass transition temperature of the reactingpolymeric mixture, which allows for a more efficient curing process andultimately results in a more uniformly polymerized product. Sufficientuniformity of the initial monomeric mixture and the polymerized productare of particular concern for silicone hydrogels, primarily due to theinclusion of silicone-containing monomers which may tend to separatefrom the hydrophilic comonomer. Suitable organic diluents include, forexample, monohydric alcohols such as C₆-C₁₀ straight-chained aliphaticmonohydric alcohols, e.g., n-hexanol and n-nonanol; diols such asethylene glycol; polyols such as glycerin; ethers such as diethyleneglycol monoethyl ether; ketones such as methyl ethyl ketone; esters suchas methyl enanthate; and hydrocarbons such as toluene. Preferably, theorganic diluent is sufficiently volatile to facilitate its removal froma cured article by evaporation at or near ambient pressure. Generally,the diluent is included at about 5 to about 60 percent by weight of themonomeric mixture, with about 10 to about 50 percent by weight beingespecially preferred.

Solvent removal can be accomplished by evaporation at or near ambientpressure or under vacuum. An elevated temperature can be employed toshorten the time necessary to evaporate the diluent. The time,temperature and pressure conditions for the solvent removal step willvary depending on such factors as the volatility of the diluent and thespecific monomeric components, as can be readily determined by oneskilled in the art. According to a preferred embodiment, the temperatureemployed in the removal step is preferably at least about 50° C., forexample, about 60° C. to about 80° C. A series of heating cycles in alinear oven under inert gas or vacuum may be used to optimize theefficiency of the solvent removal. The cured article after the diluentremoval step should contain no more than twenty percent by weight ofdiluent, preferably no more than about 5 percent by weight or less.

Following removal of the organic diluent, the lens can then be subjectedto mold release and optional machining operations. The machining stepincludes, for example, buffing or polishing a lens edge and/or surface.Generally, such machining processes may be performed before or after thearticle is released from a mold part. Preferably, the lens is dryreleased from the mold by employing vacuum tweezers to lift the lensfrom the mold, after which the lens is transferred by means ofmechanical tweezers to a second set of vacuum tweezers and placedagainst a rotating surface to smooth the surface or edges. The lens maythen be turned over in order to machine the other side of the lens

Next, the lens will be immersed in an aqueous packaging solution andstored in a packaging system according to the present invention.Generally, a packaging system for the storage of an ophthalmic lensaccording to the present invention includes at least a sealed containercontaining one or more unused ophthalmic lens immersed in an aqueouspackaging solution. Preferably, the sealed container is a hermeticallysealed blister-pack, in which a concave well containing a contact lensis covered by a metal or plastic sheet adapted for peeling in order toopen the blister-pack. The sealed container may be any suitablegenerally inert packaging material providing a reasonable degree ofprotection to the lens, preferably a plastic material such aspolyalkylene, PVC, polyamide, and the like.

Hyaluronic acid, also known as hyalurate or hyaluronan, belongs to thegroup of glycosaminoglycans. In general, hyaluronic acid is a highmolecular weight polysaccharide with an unbranched backbone composed ofalternating sequences of β-(1-4)-glucoronic acid and β-(1-3)-N-acetylglucosamine moieties. Each dimer is referred to as one unit and has amolecular weight of approximately 450 Daltons (D). The hyaluronic acidfor use herein can have a number average molecular weight of from about10,0000 to about 10,000,000, preferably from about 50,000 to about2,000,000 and most preferably from about 100,000 to about 1,000,000. Anexample of a salt of hyaluronic acid is hyaluronic acid sodium salt.

The amount of hyaluronic acid or salt thereof employed is that amounteffective to improve the surface properties of the ophthalmic devicewhen combined with a non-ionic polyol. Generally, the concentration ofthe hyaluronic acid present in the packaging solution of the inventionis from about 0.001 to about 1% w/w, preferably from about 0.05 to about0.5% w/w and most preferably from about 0.1 to about 0.3% w/w.

The aqueous packaging solutions according to the present invention arephysiologically compatible. Specifically, the solution must be“ophthalmically safe” for use with a lens such as a contact lens,meaning that a contact lens treated with the solution is generallysuitable and safe for direct placement on the eye without rinsing, thatis, the solution is safe and comfortable for daily contact with the eyevia a contact lens that has been wetted with the solution. Anophthalmically safe solution has a tonicity and pH that is compatiblewith the eye and includes materials, and amounts thereof, that arenon-cytotoxic according to ISO standards and U.S. Food & DrugAdministration (FDA) regulations. The solutions of the present inventionwill also have a viscosity ranging from at least about 1 cps, preferablyat least about 2 cps and most preferably at least about 4 cps. In oneembodiment, the solutions of the present invention do not contain asurfactant such as a non-ionic surfactant, e.g., poloxamer.

The solution of the present invention should also be sterile in that theabsence of microbial contaminants in the product prior to release mustbe statistically demonstrated to the degree necessary for such products.The liquid media useful in the present invention are selected to have nosubstantial detrimental effect on the lens being treated or cared forand to allow or even facilitate the present lens treatment ortreatments. The liquid media are preferably aqueous-based. Aparticularly useful aqueous liquid medium is that derived from saline,for example, a conventional saline solution or a conventional bufferedsaline solution.

The pH of the present solutions should be maintained within the range ofabout 4 to about 9, and preferably about 6.5 to about 7.8. Suitablebuffers may be added, such as boric acid, sodium borate, potassiumcitrate, citric acid, sodium bicarbonate,tris(hydroxymethy)aminomethane, and various mixed phosphate buffers(including combinations of Na₂ HPO₄, NaH₂ PO₄ and KH₂ PO4) and mixturesthereof. Generally, buffers will be used in amounts ranging from about0.05 to about 2.5 percent by weight, and preferably from about 0.1 toabout 1.5 percent by weight of the solution.

Typically, the solutions of the present invention are also adjusted withtonicity agents, to approximate the osmotic pressure of normal lacrimalfluids which is equivalent to a 0.9 percent solution of sodium chlorideor 2.5 percent of glycerol solution. The solutions are madesubstantially isotonic with physiological saline used alone or incombination, otherwise if simply blended with sterile water and madehypotonic or made hypertonic the lenses will lose their desirableoptical parameters. Correspondingly, excess saline may result in theformation of a hypertonic solution which will cause stinging and eyeirritation.

Examples of suitable tonicity adjusting agents include, but are notlimited to, sodium and potassium chloride, dextrose, glycerin, calciumand magnesium chloride and the like and mixtures thereof. These agentsare typically used individually in amounts ranging from about 0.01 toabout 2.5% w/v and preferably from about 0.2 to about 1.5% w/v.Preferably, the tonicity agent will be employed in an amount to providea final osmotic value of at least about 200 mOsm/kg, preferably fromabout 200 to about 400 mOsm/kg, more preferably from about 250 to about350 mOsm/kg, and most preferably from about 280 to about 320 mOsm/kg.

If desired, one or more additional components can be included in thepackaging solution. Such additional component or components are chosento impart or provide at least one beneficial or desired property to thepackaging solution. Such additional components may be selected fromcomponents which are conventionally used in one or more ophthalmicdevice care compositions. Examples of such additional components includecleaning agents, wetting agents, nutrient agents, sequestering agents,viscosity builders, contact lens conditioning agents, antioxidants, andthe like and mixtures thereof. These additional components may each beincluded in the packaging solutions in an amount effective to impart orprovide the beneficial or desired property to the packaging solutions.For example, such additional components may be included in the packagingsolutions in amounts similar to the amounts of such components used inother, e.g., conventional, contact lens care products.

Useful sequestering agents include, but are not limited to, disodiumethylene diamine tetraacetate, alkali metal hexametaphosphate, citricacid, sodium citrate and the like and mixtures thereof.

Useful viscosity builders include, but are not limited to, hydroxyethylcellulose, hydroxymethyl cellulose, polyvinyl pyrrolidone, polyvinylalcohol and the like and mixtures thereof.

Useful antioxidants include, but are not limited to, sodiummetabisulfite, sodium thiosulfate, N-acetylcysteine, butylatedhydroxyanisole, butylated hydroxytoluene and the like and mixturesthereof.

The method of packaging and storing an ophthalmic lens such as asilicone hydrogel contact lens according to the present inventionincludes at least packaging a silicone hydrogel contact lens immersed inthe aqueous packaging solution described above. The method may includeimmersing the ophthalmic lens in an aqueous packaging solution prior todelivery to the customer/wearer, directly following manufacture of thecontact lens. Alternately, the packaging and storing in the solution ofthe present invention may occur at an intermediate point before deliveryto the ultimate customer (wearer) but following manufacture andtransportation of the lens in a dry state, wherein the dry lens ishydrated by immersing the lens in the solution. Consequently, a packagefor delivery to a customer may include a sealed container containing oneor more unused ophthalmic lenses immersed in an aqueous packagingsolution according to the present invention.

In one embodiment, the steps leading to the present ophthalmic lenspackaging system includes (1) molding an ophthalmic lens in a moldcomprising a posterior and anterior mold portion, (2) removing the lensfrom the mold and hydrating the lens, (3) introducing the aqueouspackaging solution with the hyaluronic acid or salt thereof into thecontainer with the lens supported therein, and (4) sealing thecontainer. Preferably, the method also includes the step of sterilizingthe contents of the container. Sterilization may take place prior to, ormost conveniently after, sealing of the container and may be effected byany suitable method known in the art, e.g., by autoclaving of the sealedcontainer and its contents at temperatures of about 120° C. or higher.

The following examples are provided to enable one skilled in the art topractice the invention and are merely illustrative of the invention. Theexamples should not be read as limiting the scope of the invention asdefined in the claims.

In the examples, the following abbreviations are used.

I4D5S4H: Urethane prepolymer derived from isophorone diisocyanate,diethylene glycol, α,ω-bis-hydroxybutyl polydimethylsiloxane of Mn4,000, and 2-hydroxyethyl methacrylate in the approximate molar ratio of10:4:5:2

TRIS: 3-methacryloxypropyltris(trimethylsiloxy)silane

DMA: N,N-dimethylacrylamide

HEMA: 2-hydroxyethyl methacrylate

NVP: N-vinyl-2-pyrrolidone

HEMAVC: methacryloxyethyl vinyl carbonate

D1173: 2-hydroxy-2-methyl-1-phenylpropan-1-one (available as Darocur1173 initiator)

IMVT: 1,4-bis(4-(2-methacryloxyethyl)phenylamino)anthraquinone

EXAMPLE 1

Lens casting of a polyurethane-siloxane hydrogel formulation

Silicone hydrogel lenses were prepared from the monomer mixture setforth below in Table 1. The monomer mixture was filtered, cast betweenanterior and posterior polypropylene mold parts and then cured under UVfor 1 hour. After being released from the molds, the lenses wereextracted with isopropanol overnight, and then hydrated in deionized(DI) water.

TABLE 1 Formulation Prepolymer Example 1 I4D5S4H   53 parts by weightTRIS   15 parts by weight DMA    9 parts by weight HEMA    5 parts byweight NVP   24 parts by weight HEMAVC  1.3 parts by weight n-Hexanol  10 parts by weight D1173  0.5 parts by weight IMVT 0.015 parts byweight

EXAMPLE 2

Surface treatment with hyaluronic acid sodium salt solution.

An aqueous solution containing 0.5% by weight of hyaluronic acid sodiumsalt (HA) (hyaluronic acid sodium salt from Streptococcus equi,commercially available from Fluka Biochemika, having a total impuritycontent of less than 1% protein and a solubility of 5 mg/ml in water)was prepared, and the pH was adjusted to 4 using dilute hydrochloricacid. The lenses prepared in accordance with Example 1 were then placedin glass vials, filled with the aqueous treating solution containing0.5% by weight HA. Next, the lenses were autoclaved for 1 cycle (121°C., 30 minutes) and kept at 45° C. for 24 hours. The lenses were takenout and shaken with large amounts of DI water and then saved in a boratebuffer saline for testing. The lenses thus obtained were visuallyexamined and appeared more wettable than the control lens. The lenseswere also rubbed between fingers and felt more lubricious than thecontrol lens. The control lens was a lens from Example 1 which wasautoclaved in DI water for 1 cycle and stored in a borate buffer salinefor testing.

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore the above description should notbe construed as limiting, but merely as exemplifications of preferredembodiments. For example, the functions described above and implementedas the best mode for operating the present invention are forillustration purposes only. Other arrangements and methods may beimplemented by those skilled in the art without departing from the scopeand spirit of this invention. Moreover, those skilled in the art willenvision other modifications within the scope and spirit of the featuresand advantages appended hereto.

1. A method of preparing a package comprising a storable, sterileophthalmic device, the method comprising: (a) immersing an ophthalmicdevice in an aqueous packaging solution comprising hyaluronic acid orsalt thereof, wherein the aqueous packaging solution has an osmolalityof at least about 200 mOsm/kg and a pH in the range of about 4 to about9; (b) packaging the solution and the device in a manner preventingcontamination of the lens by microorganisms; and (c) sterilizing thepackaged solution and device.
 2. The method of claim 1, wherein theophthalmic device is a contact lens.
 3. The method of claim 1, whereinthe ophthalmic device is a silicone hydrogel contact lens.
 4. The methodof claim 1, wherein the hyaluronic acid or salt thereof has a numberaverage molecular weight of about 10,000 to about 10,000,000.
 5. Themethod of claim 1, wherein the hyaluronic acid or salt thereof has anumber average molecular weight of about 50,000 to about 2,000,000. 6.The method of claim 1, wherein the hyaluronic acid or salt thereof has anumber average molecular weight of about 100,000 to about 1,000,000. 7.The method of claim 1, wherein the concentration of the hyaluronic acidor salt thereof in the aqueous packaging solution is about 0.001 toabout 1% w/w.
 8. The method of claim 1, wherein the concentration of thehyaluronic acid or salt thereof in the aqueous packaging solution isabout 0.05 to about 0.5% w/w.
 9. The method of claim 1, wherein theconcentration of the hyaluronic acid or salt thereof in the aqueouspackaging solution is about 0.1 to about 0.3% w/w.
 10. The method ofclaim 1, wherein the aqueous packaging solution further comprises abuffering agent.
 11. The method of claim 1, further comprisinghermetically sealing the ophthalmic device and the aqueous packagingsolution in the package.
 12. The method of claim 11, wherein heatsterilization is performed subsequent to sealing of the package.
 13. Themethod of claim 1, wherein the aqueous packaging solution does notcontain an effective disinfecting amount of a disinfecting agent. 14.The method of claim 1, wherein the aqueous packaging solution does notcontain a germicide compound.
 15. The method of claim 1, wherein theaqueous packaging solution does not contain a surfactant.
 16. The methodof claim 13, wherein the aqueous packaging solution further does notcontain a surfactant.
 17. A packaging system for the storage of anophthalmic device comprising a sealed container containing one or moreunused ophthalmic device immersed in an aqueous packaging solutioncomprising hyaluronic acid or a salt thereof, wherein the solution hasan osmolality of at least about 200 mOsm/kg, a pH of about 4 to about 9and is heat sterilized.
 18. The packaging system of claim 17, whereinthe ophthalmic device is a contact lens.
 19. The packaging system ofclaim 17, wherein the ophthalmic device is a silicone hydrogel contactlens.
 20. The packaging system of claim 17, wherein the hyaluronic acidor salt thereof has a number average molecular weight of about 10,000 toabout 10,000,000.
 21. The packaging system of claim 17, wherein thehyaluronic acid or salt thereof has a number average molecular weight ofabout 50,000 to about 2,000,000.
 22. The packaging system of claim 17,wherein the hyaluronic acid or salt thereof has a number averagemolecular weight of about 100,000 to about 1,000,000.
 23. The packagingsystem of claim 17, wherein the concentration of the hyaluronic acid orsalt thereof in the aqueous packaging solution is about 0.001 to about1% w/w.
 24. The packaging system of claim 17, wherein the concentrationof the hyaluronic acid or salt thereof in the aqueous packaging solutionis about 0.05 to about 0.5% w/w.
 25. The packaging system of claim 17,wherein the concentration of the hyaluronic acid or salt thereof in theaqueous packaging solution is about 0.1 to about 0.3% w/w.
 26. Thepackaging system of claim 17, wherein the aqueous packaging solutionfurther comprises a buffering agent.
 27. The packaging system of claim17, wherein the package is heat sterilized subsequent to sealing of thepackage.
 28. The packaging system of claim 17, wherein the aqueouspackaging solution does not contain an effective disinfecting amount ofa disinfecting agent.
 29. The packaging system of claim 17, wherein theaqueous packaging solution does not contain a germicide compound. 30.The packaging system of claim 17, wherein the aqueous packaging solutiondoes not contain a surfactant.
 31. The packaging system of claim 28,wherein the aqueous packaging solution further does not contain asurfactant.
 32. A method of treating an ophthalmic lens, the methodcomprising storing the lens in an aqueous packaging solution comprisinghyaluronic acid or a salt thereof, wherein the aqueous packagingsolution does not contain an effective disinfecting amount of adisinfecting agent.